Abstract:

The present application provides a drug-delivery device comprising a drug
reservoir chamber 16, containing a substance to be delivered, in fluid
connection with a drug administration means 18, and an
electrically-controlled battery unit 10 comprising at least one
displacement-generating battery cell 19 coupled to the drug reservoir
chamber 16 by a coupling means 14, the arrangement being such that the
displacement derived from the battery unit 10 is conveyed by the coupling
means 14 to the drug reservoir chamber 16 such that the substance is
expelled from the drug reservoir chamber 16 towards the drug
administration means 18.

Claims:

1. A drug-delivery device comprising a drug reservoir chamber, containing
a substance to be delivered, in fluid connection with a drug
administration means, and an electrically-controlled battery unit
comprising at least one displacement-generating battery cell coupled to
said drug reservoir chamber by a coupling means, the arrangement being
such that the displacement derived from said battery unit is conveyed by
said coupling means to said drug reservoir chamber such that said
substance is expelled from said drug reservoir chamber towards said drug
administration means.

2. A drug-delivery device according to claim 1 wherein said drug
administration means is selected from the group consisting of cannulas,
cannula arrays, needle, micro-needle arrays, exit ports and transdermal
patches.

3. A drug-delivery device according to claim 1 wherein each of said at
least one displacement-generating battery cells comprises at least one
volume-changing element.

4. A drug-delivery device according to claim 1 wherein the volume of each
of said at least one displacement-generating battery cells is changed as
its respective electrical capacity is changed.

5. A drug-delivery device according to claim 3 wherein each of said at
least one displacement-generating battery cells employs a chemical
reaction system based on electrochemical insertion of metal ions.

6. A drug-delivery device according to claim 5 wherein each of said at
least one displacement-generating battery cells employs a chemical
reaction system chosen from the group including Li--Sn,
(Li)LiC6--Sn, Fe--LaNis, lithium-lead, lithium-antimony,
lithium-silicon and lithium-bismuth.

7. A drug-delivery device according to claim 1 wherein said battery unit
serves to power at least some of the electrical and electronic elements
of said device.

8. A drug-delivery device according to claim 1 where said coupling means
is mechanical.

9. A drug-delivery device according to claim 8 where said coupling means
involves a displaceable wall applying direct displacement from said
battery unit to said drug chamber.

10. A drug delivery device according to claim 9 where said coupling means
is a common wall of the battery cell and the drug reservoir.

11. A drug-delivery device according to claim 8 where said coupling means
involves a displaceable wall applying indirect displacement from said
battery unit to said drug chamber.

12. A drug-delivery device according to claim 1 where said coupling means
is hydraulic.

13. A drug-delivery device according to claim 1 wherein said drug-delivery
device is disposable.

14. A drug-delivery device according to claim 1 wherein some parts of the
said drug-delivery device are disposable.

15. A drug-delivery device according to claim 1 wherein said drug-delivery
device is an implantable device.

16. A drug-delivery device according to claim 1 wherein said drug-delivery
device further comprises a filling means.

17. A drug-delivery device according to claim 1 wherein said drug-delivery
device further comprises a battery recharging means.

18. A drug-delivery device according to claim 1 wherein said drug-delivery
device is a multiple-use device-.

19. A drug-delivery device according to claim 1 wherein said drug-delivery
device is a patch-type pump.

20. A drug-delivery device according to claim 19 wherein said patch-type
pump is attached to the body of a user by a means comprising an adhesion
means, a strap, a clasp and combinations thereof.

21. A drug-delivery device according to claim 1 wherein said drug-delivery
device further comprises auto-insertion means of the administration
means.

22. A drug-delivery device according to claim 21 wherein said
auto-insertion means serves to insert the administration means.

24. A drug-delivery device according to claim 1 wherein said drug-delivery
mechanism further comprises a plurality of drug chambers containing
different drug components.

25. A drug-delivery device according to claim 24 wherein said
drug-delivery device includes means for the mixing of said different drug
components from said plurality of drug chambers.

26. A drug-delivery device according to claim 1 wherein said drug-delivery
device further comprises a plurality of battery cells.

27. A drug-delivery device according to claim 15 wherein said drug chamber
includes means enabling the intake of body fluids; said fluids serving to
dilute a drug for subsequent administration by said drug-delivery device
on reversion to its normal operating mode.

28. A drug-delivery device according to claim 27 wherein said device
further comprises means for sampling body fluids for analysis.

29. A drug-delivery device according to claim 1 wherein said drug-delivery
device further comprises communications means to remote devices, said
communications means being selected from the group consisting of magnetic
induction, infra-red, and RF devices.

30. A drug-delivery device according to claim 2 wherein said
administration means further comprises a safety feature to protect
against accidental contact or injury.

31. A drug-delivery device according to claim 1, wherein said drug
reservoir chamber is coupled to said battery unit via a displaceable
wall; such that the volume change from said battery unit serves to
control the rate of delivery of the drug.

32. A drug-delivery device according to claim 1, wherein said drug
reservoir chamber is coupled to said battery via a piston arrangement;
such that the volume change from said battery cell serves to control the
rate of delivery of the drug.

33. A drug-delivery device according to claim 1 wherein said battery cell
is a lithium-tin battery cell where the volume change in the tin
electrode on discharge of said cell causes the direct displacement of a
displaceable wall of the drug chamber.

34. A drug delivery device according to claim 1 where the pressure in the
drug chamber is monitored as part of the control and safety logic of the
system.

35. A drug delivery device according to claim 1 wherein said device is
selected from the group consisting of implantable devices, slow-infusion
devices, disposable infusion devices, partially-disposable infusion
devices and patchpumps attached to the skin.

36. A drug delivery device according to claim 1 wherein said displacement
generating battery is a primary cell.

37. A drug delivery device according to claim 1 wherein said displacement
generating battery is a secondary cell.

38. A drug delivery device according to claim 1 wherein at least one
component of the battery unit undergoes a volume change of at least
200/0.

39. A drug delivery device according to claim 1 wherein at least one
component of the battery unit undergoes a volume change of at least 30%.

40. A drug delivery device according to claim 1 wherein said drug chamber
is provided with a rigid displaceable wall section.

41. A drug delivery device according to claim 1 wherein said drug chamber
is provided with a flexible displaceable wall section.

42. A drug delivery device according to claim 1 wherein the displacement
derived from said battery unit exerts a force of at least 1 kg/sq.

43. A drug delivery device according to claim 1 wherein the displacement
derived from said battery unit exerts a force of at least 10 kg/sq.

44. A displacement-generating battery cell for driving a drug-delivery
device and comprising at least one volume-changing element, said cell
comprising a housing formed according to a concertina-shaped design with
folds in the walls thereof and containing an internal chemical reaction
system, the arrangement of said chemical reaction system being such that
as the cell is discharged, said volume-changing element expands, thereby
lengthening the battery and thus reducing the extent of said folds, such
that the cell becomes taller to reflect the expansion of said
volume-changing component.

Description:

FIELD OF THE INVENTION

[0001]The present invention relates to the field of drug-delivery and
relates to a drug-delivery device driven by an electrically-controlled
displacement-generating battery cell. More particularly, this invention
relates to a displacement-generating battery cell which drives a
drug-delivery mechanism, wherein the delivery rate can be very precisely
controlled by an electrical circuit.

BACKGROUND OF THE INVENTION

[0002]In the field of battery cells, the volume change generated as the
battery charges or discharges is a known yet undesirable side effect,
said effect being mentioned in the prior art. For example, US Patent
Application 20040115530 describes a method of preventing the detrimental
effects of the volume change of the active material in a lead-acid
battery cell. In a co-pending patent application IL169,807 by some of the
same inventors of this application, herein incorporated by reference, the
concept of making use of such so-called "undesirable" volume changes in
order to drive a drug-delivery device is described. However, said
co-pending application exploits a relatively small volume change (of the
order of 10%) as known from traditional battery chemistries, and thus
requires a hydraulic or other coupling mechanism in order to exploit the
relatively small volume change in an effective manner.

[0003]Accordingly, the achievement of a novel battery cell capable of a
significant volume change (that is one capable of effectively driving a
drug delivery device and herein referred to as a "displacement-generating
battery") allows for a unique, beneficial, simpler and therefore more
inexpensive solution for drug-delivery devices to be attained. Notably,
such a drug-delivery device, in its simplest embodiment, would not
require any mechanical or hydraulic amplification and thus would
represent an advance in the art, as it would enable direct displacement
of a drug in a reservoir within said drug-delivery device by said battery
cell. In addition, since the displacement generated by said battery is
directly related to the accumulated electric discharge in the battery,
the extent of the displacement of a drug in a reservoir can be very
accurately controlled.

[0004]It is therefore the object of the present invention to provide a
drug-delivery device driven by such a displacement-generating battery.

[0005]It is still further object of the present invention to provide a
drug-delivery device whose delivery rate and volume of drug delivered is
accurately controlled by an electrochemical reaction, and specifically,
by an electrochemical reaction that causes a volume change that actuates
the delivery of the drug.

[0006]It is still further object of the present invention to provide a
displacement-generating battery that is used as an actuator which
transmits a displacement resulting from an electrochemical reaction via a
coupling component in such a manner that a drug contained within a drug
reservoir affected by the coupling is forced through an administration
means into the body of a patient.

[0007]It is a further object of the invention that said drug-delivery be
relatively insensitive to temperature and ambient pressure changes.

[0008]It is a still further object of this invention to provide a
drug-delivery device with a minimum of moving parts.

[0009]It is a still further object of this invention to provide a
drug-delivery device where the displacement of the drug chamber can be
inherently determined from the state of discharge of the battery.

[0010]It is a still further object of this invention to provide a
drug-delivery device which does not suffer from a lag in response time.

[0011]It is a still further object of this invention to provide a
drug-delivery device which is inherently waterproof.

[0012]It is still further object of the present invention to provide a
drug-delivery device where control and maintenance issues are simpler
than in existing approaches and with less potential failure modes.

[0013]It is still further object of the present invention to provide a
drug-delivery device in which the displacement-generating battery also
provides the power to operate the electronics of the device thus
advantageously obviating the need for having a further battery cell to
power the electronics of the drug-delivery device and so the device is
simplified, made more efficient, and lowered in cost.

[0014]These and other objects of this invention will become more evident
in the summary of the invention and in the description of the preferred
embodiment.

SUMMARY OF THE INVENTION

[0015]According to the present invention there is now provided a
drug-delivery device comprising a drug reservoir chamber, containing a
substance to be delivered, in fluid connection with a drug administration
means, and an electrically-controlled battery unit comprising at least
one displacement-generating battery cell coupled to said drug reservoir
chamber by a coupling means, the arrangement being such that the
displacement derived from said battery unit is conveyed by said coupling
means to said drug reservoir chamber such that said substance is expelled
from said drug reservoir chamber towards said drug administration means.

[0016]In preferred embodiments of the present invention each of said at
least one displacement-generating battery cells comprises at least one
volume-changing element.

[0017]Preferably the volume of each of said at least one
displacement-generating battery cells is changed as its respective
electrical capacity is changed.

[0018]In preferred embodiments of the present invention said coupling
means is mechanical.

[0019]In some embodiments of the present invention said coupling means
involves a displaceable wall applying direct displacement from said
battery unit to said drug chamber.

[0020]In especially preferred embodiments of the present invention said
coupling means is a common wall of the battery cell and the drug
reservoir.

[0021]In further preferred embodiments of the present invention, said
coupling means involves a displaceable wall applying indirect
displacement from said battery unit to said drug chamber.

[0022]In a further preferred embodiment, said coupling means is hydraulic.

[0023]Thus according to a preferred embodiment of the present invention
there is provided a delivery device for drugs or other substances (herein
a "drug-delivery device") comprising a drug reservoir chamber having at
least one displaceable wall and containing a substance to be delivered in
fluid connection with a drug administration means, and a
displacement-generating element, said element being an electric battery
unit comprising at least one displacement generating battery cells
coupled to said drug chamber by a coupling means, the arrangement being
such that a change in the volume of at least one component of the
electrochemistry of said battery unit (during discharge or charge of the
displacement-generating battery) causes a wall of the battery unit to be
displaced, which in return causes a wall of said drug chamber to be
displaced such that said substance is expelled from said drug chamber
towards said drug administration means.

[0024]In preferred embodiments of the present invention said drug
administration means is selected from the group consisting of cannulas,
cannula arrays, needle, micro-needle arrays, exit ports and transdermal
patches.

[0025]Said drug-delivery device may be employed in a number of different
configurations, including but not limited to: implantable devices,
slow-infusion devices, disposable infusion devices, partially-disposable
infusion devices and patch-pumps attached to the skin. Such drug delivery
devices are useful for delivering drugs to patients which may be humans
or other animals. Given the absence of motors and other such sensitive
components, the drug-delivery device of the present invention is
inherently simple to render waterproof. The displacement-generating
battery used in said device may be either a primary cell or a secondary
cell, or involve more than one cell. Where a primary cell is used, the
volume change is caused by its discharge, and where a secondary cell is
used, the volume change may be effected during either the charging or
discharging thereof. In either case, such a displacement-generating
battery is hereby defined as one in which at least one component of the
battery cell undergoes a volume change of at least 20% or preferably at
least 30%, as opposed to conventional batteries which are designed so
that volume changes are minimized to substantially lower values. This
volume change is then conveyed, either directly or hydraulically, to a
displaceable wall of the drug chamber, causing the drug therein to be
delivered via the administration means.

[0026]The displaceable wall of the drug chamber can take a number of
forms, including but not limited to: a rigid yet displaceable section of
the wall, a flexible or bellows type wall section, a liquid-liquid
interface and a piston. A simple example of a chamber with a displaceable
wall is a cylindrical cell with a rigid circular cap sealed against one
end by means of an elastomeric gasket, said cap being capable of moving
up or down as the charge/discharge proceeds. In all such cases, the
displaceable section of the wall moves in response to the displacement of
the wall of the displacement-generating battery. In the drug-delivery
device of the present invention, said movement serves to expel a drug
from a drug chamber in mechanical connection with said displaceable wall.

[0027]In a preferred embodiment of the present invention, the
displacement-generating battery employed within the present invention
applies direct displacement to a drug chamber wall, such that the drug
contained within said drug chamber is forced through an administration
means into the body of a patient. In a further preferred embodiment of
the present invention, the displacement-generating battery applies direct
force to a wall of a pouch or other envelope comprising the at least
partially flexible or displaceable walls of the drug chamber, such that
the drug contained within said drug chamber is forced through an
administration means into the body of a patient. In a further preferred
embodiment, the displacement-generating battery employed within the
present invention pushes a piston of a drug chamber (either directly or
via mechanical or hydraulic coupling) such that the drug contained within
said drug chamber is forced through an administration means into the body
of a patient. Said administration means can include a conventional
cannula as known in the art, or any other means whereby the drug is
introduced into the body. Such means can include arrays of short cannulas
such as the SimpleChoice® patch product (SpectRx, Inc., Norcross, Ga.,
USA), arrays of micro-needles, non-invasive transdermal devices, or auto
needle insertion means. Alternatively, where the drug-delivery device of
the present invention is an implantable one, the delivery means can be
any exit port or tube leading from the device to the required location in
the body of the patient.

[0028]The key to this drug-delivery device is a battery cell, at least one
component of which undergoes a major volume change in excess of 20% and
preferably in excess of 30% of its initial volume, either during charge
or during discharge. In some cases, the overall change in volume of the
entire battery is smaller than this amount (as one element shrinks or is
depleted while another grows), but this is not important providing that
it is still possible to mechanically exploit the volume-changing
component by mechanically supporting the displacement-generating
component while ensuring that the cell casing as a whole does not
collapse or cause any other structural problem. In this manner, the full
displacement of the displacement-generating component--in this case an
electrode--may be exploited.

[0029]In general, such electrodes will benefit from a larger surface area,
i.e. thinner sections and larger internal surface area, for example those
achieved by using a pressed, pasted or sintered porous structure or one
based on finer particles. This will allow easier access of ions for
intercalation and enable higher rate discharges. In the case of a
displacement-generating battery, not only is the degree of expansion
important, but also the force developed should be adequate for
drug-delivery. Internal stresses in the expanding electrode of at least 1
kg/sq cm and preferably 10 kg/sq cm should be attainable in the course of
discharge or charge.

[0030]In especially preferred embodiments of the present invention at
least one displacement-generating battery cells employs a chemical
reaction system based on electrochemical insertion of metal ions.

[0031]Preferably each of said at least one displacement-generating battery
cells employs a chemical reaction system chosen from the group including
Li--Sn, (Li)LiC6--Sn, Fe--LaNi5, lithium-lead,
lithium-antimony, lithium-silicon and lithium-bismuth.

[0032]Preferred electrochemical systems for said displacement-generating
battery include but are not limited to Li--Sn and (Li)LiC6--Sn; both
of which are based on the phenomenon of the increase of thickness (up to
257%) of a tin (Sn) electrode under the chemical reaction with (or
electrochemical intercalation of) Li ions. A third system, Fe--LaNi5
(basically, a kind of a metal-hydride battery), could be used due to the
expansion of the Fe electrode (estimated as 250%) during its oxidation to
FeOOH. Further candidates for anodes include alloys of lithium such as
(but not limited to) lithium-aluminum, lithium-magnesium,
lithium-aluminum-magnesium, As will be obvious to one skilled in the art,
various other displacement-generating battery chemistries can be chosen
for the battery cell of this invention, subject only to the
volume-changing requirements discussed above. Further candidates for
battery systems include lithium-lead, lithium-antimony, lithium-silicon,
lithium-bismuth and fuel cells; providing only that they achieve the
volume-changing requirements discussed above. In the case of fuel cell
batteries, the volume depletion of the fuel provides the volume-changing
element.

[0033]Lithium based batteries use organic solvents or a polymer
electrolyte together with a lithium ion-providing salt. Suitable
non-limiting examples of such organic solvents include propylene
carbonate, tetrahydrofuran, 2-methyl tetrahydrofuran, gamma-butrolactone,
ethylene carbonate, dimethoxy ethane, dioxolane, diethyl carbonate,
dimethyl carbonate, ethylmethyl carbonate, and various combinations of
such solvents. Suitable non-limiting examples of electrolyte salts for
such organic solvents include lithium perchlorate, lithium
hexafluoroaresenate, lithium hexafluorophosphae, lithium
tertrfluoroborate, LiCF3SO3, and LiN(CF3SO2)2.
In all these systems, as the discharge or charge proceeds, there is
either a net volume change of the system or a large volume change in at
least one electrode. Variations on the above systems may use
lithium-carbon, lithium-graphite or lithium-aluminum alloys in place of
the lithium electrode. An example of an electrolyte for the lithium-tin
system is a solvent of a mixture of ethylene carbonate and ethyl methyl
carbonate with dissolved lithium hexafluorophosphate as the ion-providing
(ionizing) salt. Other lithium ion conducting electrolyte types are
applicable, such as gel, polymer or solid state electrolytes. The basic
volume change in these systems occurs as a result of lithium ion
intercalation from the lithium electrode into the other electrode during
the electrochemical reaction, which is driven by the potential difference
between the electrodes. In the case of a lithium-tin battery, the tin
electrode can expand by up to 257% in volume during discharge, while
generating stresses of 15 kg/sq cm. This electrode expansion can be
understood by comparing the densities of lithium (0.53) and tin (7.3).
Where the electrochemical reaction within the displacement-generating
battery is a reversible one, a battery cell of this type can also allow
refilling of the drug-delivery device.

[0034]This approach to drug-delivery device design has a number of
advantages. As there is no pump or motor in the conventional sense, there
are very few parts, and essentially only a coupling component such as a
displaceable wall between the cell and the drug chamber is a moving part.
By using a minimum number of moving parts, failure modes and maintenance
issues are minimized. Additionally, factors such as noise, friction,
backlash and assembly tolerance issues are minimized. Accordingly, very
precise control of the drug-delivery device is enabled by this design. In
fact, providing that the non-displaceable walls of the battery remain
rigid, the resolution of the achievable movement is limited only by the
accuracy of the charge/discharge circuitry; something which can be
provided to a very high degree using electronic circuitry known in the
art. This is especially important in the case of implantable
drug-delivery devices, where drug-delivery rates in the picoliter range
per minute are required so as to be able to deliver drug quantities in
the milliliter range over a period of months or years. Additionally,
advantageously this approach provides the ability to determine the volume
of drug delivered, purely by integrating the electric charge (that is,
the current per unit time) used during charge or discharge of the
battery. Despite this, it should be apparent to one skilled in the art
that, where required, it is possible to further provide (a) a closed-loop
or feedback control where which incorporates position-detection elements
such that the information concerning the volume of drug delivered is not
solely dependent on monitoring the charge/discharge performed; and (b)
pressure sensors and other feedback and safety means can be incorporated
into said control circuitry and logic.

[0035]In preferred embodiments said drug-delivery device further comprises
a battery recharging means. In said embodiments, said drug-delivery
device is a multiple-use device.

[0036]In some embodiments of the present invention, said drug-delivery
device is a patch-type pump.

[0037]In said embodiments said patch-type pump is preferably attached to
the body of a user by a means comprising an adhesion means, a strap, a
clasp and combinations thereof.

[0038]In other embodiments of the present invention, said drug-delivery
device further comprises auto-insertion means of the administration
means.

[0039]In said other embodiments, said auto-insertion means preferably
serves to insert the administration means.

[0040]In said other embodiments, said auto-insertion means preferably
automatically activates the drug-delivery device.

[0041]In further preferred embodiments of the present invention said
drug-delivery mechanism further comprises a plurality of drug chambers
containing different drug components.

[0042]In said further preferred embodiments said drug-delivery device
preferably includes means for the mixing of said different drug
components from said plurality of drug chambers.

[0043]In especially preferred embodiments of the present invention said
drug-delivery device further comprises at least one battery cell.

[0044]Preferably said drug chamber includes means enabling the intake of
body fluids; said fluids serving to dilute a drug for subsequent
administration by said drug-delivery device on reversion to its normal
operating mode.

[0045]In other embodiments of the present invention said device further
comprises means for sampling body fluids for analysis.

[0046]In still further embodiments said drug-delivery device further
comprises communications means to remote devices, said communications
means being selected from the group consisting of magnetic induction,
infra-red, and RF devices.

[0047]In preferred embodiments of the present invention said
administration means further comprises a safety feature to protect
against accidental contact or injury.

[0048]In especially preferred embodiments of the present invention, said
drug reservoir chamber is coupled to said battery unit via a displaceable
wall; such that the volume change from said battery unit serves to
control the rate of delivery of the drug.

[0049]In other preferred embodiments of the present invention said drug
reservoir chamber is coupled to said battery via a piston arrangement;
such that the volume change from said battery cell serves to control the
rate of delivery of the drug.

[0050]Preferably said at least one battery cell is a lithium-tin battery
cell where the volume change in the tin electrode on discharge of said
cell causes the direct displacement of a displaceable wall of the drug
chamber.

[0051]In preferred embodiments of the present invention the pressure in
the drug chamber is monitored as part of the control and safety logic of
the system.

[0052]The invention will now be described in connection with certain
non-limitative preferred embodiments, with reference to the following
illustrative figures so that it may be more fully understood.

[0053]With specific reference now to the figures in detail, it is stressed
that the particulars shown are by way of example and for purposes of
illustrative discussion of the preferred embodiments of the present
invention only and are presented in the cause of providing what is
believed to be the most useful and readily understood description of the
principles and conceptual aspects of the invention. In this regard, no
attempt is made to show structural details of the invention in more
detail than is necessary for a fundamental understanding of the
invention, the description taken with the drawings making apparent to
those skilled in the art how the several forms of the invention may be
embodied in practice.

[0054]Additional objects and advantages of the invention are set forth
herein, or will be apparent to those of ordinary skill in the art from,
the detailed description as follows. Also, it should be further
appreciated that modifications and variations to the specifically
illustrated and discussed features and materials hereof may be practiced
in various embodiments and uses of this invention without departing from
the spirit and scope thereof, by virtue of present reference thereto.
Such variations may include, but are not limited to, substitutions of the
equivalent steps, means, features, and materials for those shown or
discussed, and the functional or positional reversal of various steps,
parts, features, or the like.

[0055]Still further, it is to be understood that different embodiments, as
well as different presently preferred embodiments, of this invention, may
include various combinations or configurations of presently disclosed
steps, features, elements, or their equivalents (including combinations
of steps, features or configurations thereof not expressly shown in the
figures or stated in the detailed description).

BRIEF DESCRIPTION OF THE DRAWINGS

[0056]The invention is herein described, by way of example only, with
reference to the accompanying drawings, wherein:

[0057]FIG. 1 provides a block diagram of the overall drug-delivery device,
showing its main components;

[0058]FIG. 2 provides cross-sectional and isometric views of a preferred
embodiment of the drug-delivery device with a displaceable wall between
the battery cell and the drug chamber;

[0059]FIG. 3 provides cross-sectional and isometric views of a preferred
embodiment of a battery cell for use within the present invention;

[0060]FIG. 4 provides cross-sectional and isometric views showing the
integration of a number of different administration means into the
drug-delivery device; and

[0061]FIG. 5 shows isometric and cross-sectional views of additional
preferred embodiments of the drug-delivery device, including one in the
form of a pen and one in which there is hydraulic coupling between the
battery cell and the drug chamber.

DETAILED DESCRIPTION OF THE DRAWINGS

[0062]The present invention will be described in detail according to the
preferred embodiments illustrated in the accompanying drawings. Like
reference numerals are used to identify identical components in the
various views.

[0063]Referring to FIG. 1a, a simplified block diagram of the
drug-delivery device of the present invention is shown so as to
illustrate the main components involved. In this illustrative embodiment,
a battery cell 10 is shown adjacent to a drug chamber 16 with a
displaceable wall 14 between them, such that expansion of the
volume-changing component 19 of the battery 10 causes said displaceable
wall 14 to decrease the volume of the drug chamber 16. The battery 10 is
activated and controlled by the control circuit 12; the activation of
said battery 10 causing its volume-changing component 19 to expand in
this example. Said expansion causes the drug chamber 16 to contract such
that the drug is expelled through the drug administration means 18. In a
preferred embodiment, said expulsion takes place via a valve 15 leading
to drug administration means 18. Referring now to FIG. 1b, the situation
after the battery 10 has been activated is shown, illustrating the
significant change in volume of its volume-changing component 19. Note
that, depending on the battery chemistry, the electric circuit will
either discharge the battery 10 in order to cause the volume change, or
charge the battery in order to achieve this change. For this reason both
a battery and a resistor are shown within the block diagram of said
circuit 12 for a schematic representation of its functionality. If the
depletion method is used, advantageously this obviates the need for
having a further battery cell to power the drug-delivery device of the
present invention as the device is thereby self-powered to some extent,
further reducing costs. Note also that the volume-changing component 19
of the battery cell 10 does not have to be an expanding component as
shown but could, by a slightly different mechanical arrangement be a
contracting component.

[0064]Referring now to FIG. 2, a cross-sectional view of a preferred
embodiment of the drug-delivery device of the present invention is
provided. FIG. 2a shows the configuration prior to activating the
battery, while FIG. 2b shows the configuration of this device at the end
of the device's operation. This embodiment comprises a housing 20 which
contains the battery 10 and a drug chamber 16. In this embodiment, the
expansion of the battery 10 moves a coupling means 25 in a shape of a
plate which in turn displaces the displaceable wall 14 and reduces the
volume of the drug chamber 16, causing the drug to be expelled via the
administration means 18. In the preferred embodiment shown, said plate 25
is covered by a displaceable wall 14 of the drug chamber 16, said
displaceable wall 14 incorporating a bellows-shaped circumference. In
this preferred embodiment, the use of the displaceable wall 14 in this
manner enables the optimal use of the drug chamber 16 shape in that said
chamber 16 can be almost completely depleted by the displacement of said
plate 25. Additionally, the bellows section of this displaceable wall 14
provides a counter-force to the force generated by the cell 10, ensuring
that the displacement produced operates in a controlled fashion and is
less susceptible to motion artifacts. As will be obvious to one skilled
in the art, such a counter-pressure effect can alternatively be performed
by the use of any other counter pressure means including but not limited
to springs, or other compressible elements. The volume change under the
displaceable wall 14 will be compensated either by having an opening (not
shown) to the ambient air through the bottom side of the housing 20 or by
using any other volume compensation means known in the art. An electronic
control unit 12, which controls the discharge of the battery 10 is
further incorporated in the drug-delivery device. Said control unit 12
may be interfaced with a pressure sensor (not shown) located either
within the drug chamber 16, on the walls of the drug chamber 16, or along
the liquid path to the administration means 18, in order to serve as the
occlusion detector and send a signal back to the control unit 12 to stop
the activation of the battery 10. As will be obvious to one skilled in
the art, a suitable wiring arrangement (not shown) whereby both
polarities of the cell 10 are connected to contacts attached to said
control unit 12 is provided. Suitable materials for the housing 20
include plastics including but not limited to polyethylene (PE) and
polypropylene (PP), or metal such as stainless steel; and suitable
materials for the displaceable wall 14 include stainless steel, aluminum,
rigid plastics or multilayer films.

[0065]Advantageously, this embodiment uses a small, lightweight battery 10
which has a small diameter relative to the diameter of the housing 20;
such that the resulting device is light relative to the volume of drug it
can deliver. For example the diameter of the battery 10 can be 10-30 mm,
while the diameter of the drug chamber 16 is 20-60 mm correspondingly.
Thus an amplification effect is achieved whereby a relatively narrow
piston presses upon a drug chamber of broader proportions. Note that this
does require relatively high force to be generated by the battery cell
10, but the cells described in the preferred embodiment below
successfully generate this force.

[0066]Referring now to FIG. 2c, an isometric view of the drug-delivery
device of the present invention is provided, showing the housing 20, an
electronic control unit 12 inserted into a recess in said housing and a
delivery means 18 shown here as a thin tube. The housing 20 further
comprises an air-evacuation channel (not shown) for the evacuation of air
from said recess as said control unit 12 is inserted. Said control unit
12 may be a disposable, semi-disposable or permanent one. Where it is
either semi-disposable or permanent, it may interlock with a location on
the drug-delivery device (for example as shown in the present embodiment)
so as to enable easy insertion and removal. Advantageously, making this
control unit 12 re-usable reduces the cost of using the drug-delivery
devices of the present invention, as then the cost of one control unit 12
may be spread over the use of many disposable devices. In a preferred
embodiment, said battery cell 10 is simply discharged (in a controlled
manner) by said control unit 12, making the device of the present
invention essentially self-powered. Some examples of different delivery
means suitable for use with this device are provided within the context
of FIG. 4 below. The design can be either a circular one as shown, or a
square design can be used. The unexploited space in this embodiment can,
advantageously, be used for the electrical components such as sensors,
buttons and/or a buzzer (all not shown). As will be obvious to one
skilled in the art, in a preferred embodiment, all the elements of the
drug-delivery device and its internal wiring are protected against
environmental influences such as humidity.

[0067]It will be obvious to one skilled in the art that the drug does not
have to be in direct contract with the displaceable wall 14 and the inner
surface of the housing 20, but rather can be maintained within a flexible
pouch. Suitable materials for fabricating such a drug pouch include but
are not limited to high-density polyethylene (HDPE) and polypropylene
(PP) or any type of multi-layer film including such materials. From a
regulatory perspective, this embodiment is advantageous as it enables the
drug-filling to be performed in a separately controlled and regulated
fabrication environment, while the integration of the pouch into the
complete drug-delivery device can potentially be performed in a less
controlled environment.

[0068]Referring now to FIG. 3, a preferred embodiment of the battery cell
10 which drives the drug-delivery device is shown. In a preferred
embodiment, the lithium-tin battery chemistry is employed. FIG. 3a
provides a cross-sectional view of said cell showing its internal
structure, while FIG. 3b provides a isometric view showing the
concertina-like structure formed; both showing the initial state of the
cell 10 before activation. As shown in FIG. 3a, said cell 10 comprises a
flexible metal sheet housing 35 formed according to a concertina-shaped
design; said housing 35 containing a lithium cathode 30 and a tin anode
19 which, in this embodiment, is the expanding element. The cell 10
further comprises a rigid cylindrical metallic mesh 33 which surrounds
the tin anode 19; there being also a separator (not shown) between the
lithium cathode 30 and said mesh 33. Thus the arrangement of the battery
components is a concentric cylinder one, where all the remaining volume
within the cell 10 is taken up by the electrolyte 32. In this preferred
embodiment, the electrolyte 32 used for the lithium-tin system is a
solvent of a mixture of ethylene carbonate and ethyl methyl carbonate
with dissolved lithium hexafluorophosphate as the ion-providing
(ionizing) salt. As the cell 10 is depleted, the lithium ions penetrate
the tin cathode 19 causing it to expand. In the present embodiment, said
expansion is constrained to take place primarily in the vertical
direction due to the rigidity of the mesh 33 which prevents expansion to
the sides. Said expansion therefore takes place against the rigid battery
cap 37. In this embodiment the cap 37 serves as one pole of the battery
and the housing 35 serves as the second pole. The sealing between the cap
37 and the housing 35 is electrically insulated. The wiring from the
control unit will be connected to these battery poles. The housing 35 can
be made from materials other than metal such as multilayer films as
described in patents U.S. Pat. Nos. 5,134,046, and 6,296,967) which are
non-conductive, and the wiring arrangement can be as known in the art,
for example as per U.S. Pat. No. 6,296,967.

[0069]Referring now to FIGS. 3c and 3d, the state of the battery cell 10
as it is fully depleted is shown, in cross-sectional and isometric views
respectively. Full depletion means that all the lithium ions have
migrated into the tin cathode 19, leaving only electrolyte 32 behind. The
resulting expansion of the cathode 19 has raised the position of the
battery cap 37, causing an overall change in the shape of the cell. Said
change is enabled by the flexible nature of the cell's housing 35. In the
preferred embodiment shown, the flexible concertina shape shown is
readily adaptable to the new configuration of the battery cell 10, as it
adjusts to being lengthened by reducing the extent of the folds in the
side walls and at the same time moving inwards in order to adapting to
the overall volume change in the cell In this manner, the cell 10 becomes
taller but narrower to reflect the expansion of its volume-changing
component.

[0070]Note that in this preferred embodiment, the tin cathode 19 needs to
be highly porous while also preserving mechanical strength. In a
preferred embodiment it is prepared by making a 2:1 mixture (by volume)
of Sn powder and a powder of table salt, NaCl. This mixture was
pressurized in a stainless steel mold under 5 tons of pressure to form
the appropriately sized pellet. This pellet was then boiled several times
in distilled water, with fresh portions of distilled water being used
each time, and then, finally, sonicated in distilled water for 5 minutes.
After drying and weighing the pellet, full dissolution of the NaCl was
verified. In this way, highly dispersed and highly porous, yet
mechanically stable Sn electrodes were prepared. The constraining of the
Sn pellet as it expands was solved by designing a stainless steel mesh
cylinder as a holder for this pellet. The porosity enables the lithium
ions to penetrate the tin (via the electrolyte), while the mesh controls
the direction of said expansion. Note also that in this embodiment, as
the Li is consumed, it is important to concentrate the remaining Li close
to this mesh, and thus a copper (Cu) net cylinder (not shown) surrounds
the lithium for this purpose.

[0071]As will be obvious to one skilled in the art, a number of different
embodiments of the battery cell 10 could be applied in the design of the
cell. For example, the anode 19 need not be constrained to only expand
upwards, but could alternatively be constrained to expand downwards, or
be allowed to expand in both directions simultaneously. Note that in the
preferred embodiment shown, the lithium anode 30 extends higher than the
tin cathode 19 so as to maximize the adjacent surface between the two, in
order to enhance the ion transport. However, in order to produce a lower
profile cell, an embodiment in which the initial height of both
electrodes is close to identical may be used. In this embodiment, the ion
transport is less efficient as the tin cathode 19 expands and the
protruding part of it is no longer adjacent to the lithium anode 30, but
this lack of chemical efficiency is a trade-off that may be worth making
in order to enable the drug-delivery device to be miniaturized more
effectively. In a further preferred embodiment, the arrangement of
cathode and anode may be one employing parallel layers, one above the
other; in or similar to the manner of a button cell. In a further
preferred embodiment, a multiplicity of anodes and cathodes may be used
to produce the desired displacement.

[0072]In a further embodiment the construction of the battery cell is on a
Printed Circuit Board (PCB): the electrodes will be selectively "printed"
on the circuit board in contact with conductive channels. The area of the
electrodes will be confined under a flexible first cover sealed to the
PCB and filled with electrolyte, said first cover being the displaceable
wall of the battery. In a preferred embodiment a cover is placed around
said first cover and sealed against the PCB, forming the drug chamber. It
is obvious to those skilled in the art that any fashion of coupling means
can be introduced between the displaceable wall of the battery and the
displaceable wall of the drug chamber. The control circuit can be placed
on the same PCB helping to further miniaturize the assembly and increase
reliability. This embodiment is advantageous for small drug chamber
applications where compactization is crucial such as implantable
controlled drug release devices.

[0073]Referring now to FIG. 4, a number of alternative types of
administration means 18 are shown. The administration means 18 can take
numerous forms depending on the type of application for which the
drug-delivery device of the present invention is being used. As will be
clear to one skilled in the art, the administration means 18 can be any
means whereby the drug or other substance delivered by the device enters
the patient's body, including but not limited to an exit port in an
implantable version of the device, and a cannula, cannula array or
transdermal patch for an external device. In its simplest form said
administration means is simply a conduit extending from the device.
Referring now to FIG. 4a, said conduit 50 leads to a Luer lock, which is
a standard connector to an infusion set. Alternatively, and as shown in
FIG. 4b, the Luer lock is incorporated into the housing 20 of the device.
In the further preferred embodiment shown in FIG. 4c, an isometric view
of an embodiment in which the administration means 18 is a cannula is
shown. Said cannula is in fluid connection with the drug chamber 16, and
extends either directly from the housing 20, or from a tab projecting
therefrom (not shown). Said cannula may be a rigid one or an array of
small rigid ones. In a further preferred embodiment, a flexible cannula
such as the Teflon® type cannulas known in the art may be used. In
the latter case, said cannula can be inserted into the patient's body by
means of an insertion device. In a still further preferred embodiment,
the cannula can be inserted into the body by a mechanism internal to the
drug-delivery device of the present invention.

[0074]Referring now to FIG. 4d, a side view of a further preferred
embodiment is provided. In this embodiment, the administration means 18
is an array of mini or micro-needles extending from the base of the
housing 20 of the device. This embodiment is especially suitable for a
low-profile version of the device, where only a small drug volume is
required. Examples of micro-needle arrays include the Microstructured
Transdermal Systems (MTS) array from 3M Drug-delivery Systems (St. Paul,
Minn., USA). Advantageously, this type of array enables the disruption of
the outermost layer of the skin, the stratum corneum, without causing
pain; and thus the drug device of the present invention which integrates
such an array can be applied to the skin in a completely painless manner.

[0075]In general the drug-delivery device of the present invention is
suitable for use as a patch-pump for delivering drug volumes between 0.5
mL and 10 mL. Embodiments at the lower end of this range will be more
coin-like in shape, whereas those at the higher end will be more
reminiscent of the embodiments shown in FIGS. 2 and 4. A patch-pump of
this nature can be applied to the skin in a number of manners, including
but not limited to the use of adhesives, straps and such-like. It may
also be desirable to automatically activate the drug-delivery device when
the administration means 18 is applied to the skin, or when an
auto-insertion means of a cannula is activated.

[0076]Referring now to FIGS. 5a and 5b, isometric and cross-sectional
views (respectively) are shown of a pen-shaped preferred embodiment of
the drug-delivery device of the present invention. In this preferred
embodiment, a multiplicity of battery cells 10 as described above are
arranged in series such that their combined displacement presses upon a
displaceable wall 14. Said displaceable wall 14 acts as a piston within
the drug chamber 16; the movement of said piston 14 serving to expel the
drug. In a preferred embodiment of this configuration, the pen-shape is
terminated at its upper end with a Luer lock serving as the
administration means 18, and the electronic control unit 12 is integrated
into the pen's base. This embodiment has the advantage of efficiently
exploiting the available volume, such that there is little of no "dead
space" within the device's housing. Additionally, the pen form-factor is
well known, easy to clip on to shirt or jacket and unobtrusive; while
also obviating the need to adhere the device to the skin. As will be
obvious to one skilled in the art, the relative location of the
components within the pen shape can easily be altered, and thus if it is
preferred to have the Luer lock on the bottom and the electronics at the
top, this is trivial to achieve.

[0077]A further advantage of this embodiment is that the shape of the drug
chamber 16 enables a vial with an integral piston to be used. This use of
such a vial is further described in connection with FIGS. 5c, 5d and 5e,
in which hydraulic coupling is utilized to couple the battery cell 10 to
a vial 55. This embodiment enjoys the advantage that it may use
relatively standard vials, which are typically made from glass and can
hold a drug for an extended period. Such a vial 55 may be inserted into
the device shown by the user, thereby reducing regulatory requirements in
the development of such a device. In this preferred embodiment, the
expansion of the volume-changing component of the cell 10 causes the
contraction of a reservoir 57 containing hydraulic fluid. On said
contraction, said hydraulic fluid is expelled via hydraulic conduit 56
where it presses upon a piston (not shown) at the base of said vial 55;
thereby causing the drug contained within said vial 55 to be expelled. It
will be clear to one skilled in the art that the coupling between the
battery cell 10 and the vial 55 may be achieved via any coupling means
including but not limited to mechanical bar mechanisms, mechanical
trains, pulleys, etc., resulting in either proportional motion or a more
complex exponential correlation.

[0078]It will be noted that while all the above embodiments employ an
expanding element within the battery cell, it will be clear to one
skilled in the art that the drug-delivery device could equally well be
driven by a contracting element within said cell, by changing the
mechanical operation. Examples of this approach are shown in co-pending
application IL169,807. Additionally, springs may advantageously be
incorporated into the device in a number of configurations. For example,
all the embodiments described above will achieve greater stability by
having the driving force partially counterbalanced by an opposing spring.
This will ensure smoother movement and provide greater artifact
resistance. In a further preferred embodiment, the spring can provide the
driving force while the cell serves as a brake. The advantages of this
approach and further details of its implementation are described in
co-pending published application WO2004067066 by one of the same authors;
hereby incorporated by reference. It will also be obvious to one skilled
in the art that the connection between the battery cell and the drug
chamber can be any kind of mechanical, hydraulic, magnetic or other
coupling means known in the art; and that said coupling action may result
in either a proportional or an exponential correlation between a
multiplicity of such drug chambers and a multiplicity of such cells. Note
that in certain systems according to this embodiment the driving force
will be the combination of the force exerted by the spring and the
contraction/expansion of the cell.

[0079]Whereas the embodiments above describe relatively simple
configurations of the drug-delivery device of the present invention, the
general principles involved in said invention enable the implementation
of a large number of further embodiments; said further embodiments
addressing further issues in such devices, such as refilling, drug
dilution, delivery of a multiplicity of drugs (with or without mixing)
and the fabrication of sophisticated implantable versions. For example, a
combination of two cells driving in opposite direction may be employed in
order to enable two-way motion of a drug chamber piston in order to allow
refilling of the drug chamber. Similarly, if it is desired to provide an
implantable drug-delivery device which is able to work over an extended
period, a second drug chamber containing a highly-concentrated form of
the drug to be delivered can be incorporated. In a preferred embodiment,
a small amount of said drug concentrate from the second or reservoir
chamber is introduced to the drug chamber while body fluids are also
introduced into said drug chamber to dilute it. In this way, further
described in co-pending patent application IL169,807, the drug chamber is
re-filled using a concentrate and then may resume its slow-infusion mode
of operation. As will be obvious to one skilled in the art, the
concentrated drug can be in either liquid or solid form, and the
mechanism as described above can provide drug-delivery over an extended
period without requiring external refilling. Likewise, the ability to use
the drug-delivery device of the present invention to perform intake of
body fluids enables said device to further incorporate various body fluid
sampling and/or analysis elements.

[0080]In another preferred embodiment, the drug delivery device is driven
by a displacement-generating battery, such battery increasing its volume
due to an electrochemical reaction that discharges the battery; where
such volume expansion actuates a coupling device to expel a drug from the
drug chamber via an administration means to the patient.

[0081]In yet another preferred embodiment, the drug delivery device is
driven by a displacement-generating battery containing an expanding
electrode which expands due to cell discharge and whose volume expansion
can be exploited to actuate a coupling device to expel a drug from the
drug chamber via an administration means to the patient.

[0082]Regarding the electrical or electronic control circuit of the
drug-delivery device of the present invention, it will be apparent to
those skilled in the art that a wide range of electronic control systems
(not shown) may be incorporated within (or interfaced to) said device.
Said range includes: (a) microprocessor-controlled variable-resistance or
load elements for controlled discharge of the cell; (b) removable control
units that enable a semi-disposable device to be constructed whereby all
or part of the control circuitry may be moved from disposable section to
disposable section; (c) systems comprising a remote-control element; (d)
systems that interface to a flow-control feedback element monitoring the
actual drug-delivery rate, either directly or indirectly; (e) an
interface control unit that receives signals related to medical
parameters such as blood-glucose levels, other blood-analyte levels and
body temperature; and (f) any combination of the above. Advantageously,
said electronics circuit and/or electronic control systems may be at
least partially powered by the very depletion of power that drives the
drug-delivery device, thereby in many cases obviating the need to provide
a battery to power the electronics of such a device. Additionally, in the
case of an implanted device, the design may further employ embedded
electronics sealed by resin casting or other sealing means known in the
art, and various communication means including but not limited to
magnetic coupling transmission, RF or IR transmission.

[0083]Preferred chemical systems for the battery cell of the drug-delivery
device of the present invention are those which are non-gassing or in
which there is minimal parasitic gas production. Nevertheless, in the
case that the selected chemical reaction does generate gas and the
mechanical embodiment is sensitive to gas (note that the embodiments with
high counter force are less sensitive to gas) said gas may either be
vented via a gas-permeable membrane or recombined via a catalytic plug
such as those made by Hoppecke Battery Company, Germany. As all cell
walls other than the displaceable one must remain fixed and rigid in
order to maintain the accuracy of the slow-infusion device, it is
important that such membrane be provided with an appropriate support
structure so as not to detract from the rigid structure of the cell.
These gas eliminating means are arranged in a fashion that efficiently
operates in every operational orientation of the device. Suitable
gas-permeable membranes include Fluoropore® membrane from Millipore
Inc. (Billerica, Mass., USA) and Emflon® from Pall Inc. (East Hills,
N.Y., USA).

[0084]While the invention has been shown herein in what is presently
conceived to be the most practical and preferred embodiment thereof, it
will be apparent to those of ordinary skill in the art that many
modifications may be made thereof within the scope of the invention,
which scope is to be accorded the broadest interpretation of the appended
claims so as to encompass all equivalent structures and devices.